Phosphodiesterase 5 inhibitors augment UT-15C-stimulated ATP release from erythrocytes of humans with pulmonary arterial hypertension.

Both prostacyclin analogs and phosphodiesterase 5 (PDE5) inhibitors are effective treatments for pulmonary arterial hypertension (PAH). In addition to direct effects on vascular smooth muscle, prostacyclin analogs increase cAMP levels and ATP release from healthy human erythrocytes. We hypothesized that UT-15C, an orally available form of the prostacyclin analog, treprostinil, would stimulate ATP release from erythrocytes of humans with PAH and that this release would be augmented by PDE5 inhibitors. Erythrocytes were isolated and the effect of UT-15C on cAMP levels and ATP release were measured in the presence and absence of the PDE5 inhibitors, zaprinast or tadalafil. In addition, the ability of a soluble guanylyl cyclase inhibitor to prevent the effects of tadalafil was determined. Erythrocytes of healthy humans and humans with PAH respond to UT-15C with increases in cAMP levels and ATP release. In both groups, UT-15C-induced ATP release was potentiated by zaprinast and tadalafil. The effect of tadalafil was prevented by pre-treatment with an inhibitor of soluble guanylyl cyclase in healthy human erythrocytes. Importantly, UT-15C-induced ATP release was greater in PAH erythrocytes than in healthy human erythrocytes in both the presence and the absence of PDE5 inhibitors. The finding that prostacyclin analogs and PDE5 inhibitors work synergistically to enhance release of the potent vasodilator ATP from PAH erythrocytes provides a new rationale for the co-administration of these drugs in this disease. Moreover, these results suggest that the erythrocyte is a novel target for future drug development for the treatment of PAH.

Localization and treatment of bronchopleural fistula through capnography.

Bronchopleural fistula (BPF) is a feared complication in the setting of pneumonectomy, lobectomy, and pulmonary infection. The development of BPFs significantly increases morbidity and mortality, and their treatment is complicated, multifaceted, and variable in success. Recently, the use of fibrin glues, acrylic glues, and endobronchial valves through bronchoscopy has allowed for minimally invasive treatment, sparing the patient surgical intervention. Results in the literature for these modalities have been mostly positive in a variety of clinical scenarios. Regardless of the therapeutic interventions used, proper diagnosis and localization of these fistulas is essential. These modalities have traditionally included installation of methylene blue in the pleural space, balloon occlusion, and ventilation scintigraphy. Here, we report the successful localization and treatment of a BPF through the use of localized bronchoscopic capnography in a 30-year-old woman with a complicated BPF. Initial attempts to localize the fistula with Fogarty catheter balloon occlusion were unsuccessful, as multiple segments were involved. Ultimately, with a capnographic catheter, the precise segments could be identified and subsequently occluded with acrylic glue. Air leak and pneumothorax resolved, chest tubes were removed without complication, and the patient was discharged 2 days after the procedure.